Recombinant Human Erythropoietin Improves Gut Barrier Function in a Hemorrhagic Shock and Resuscitation Rat Model
| Autor: | David K. Driman, Tao Rui, Anargyros Xenocostas, Claudio Martin, Xiujun Jiao, Capt Raymond L. C. Kao, Weixiong Huang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Resuscitation Mean arterial pressure Cell Membrane Permeability medicine.medical_treatment Hemodynamics Shock Hemorrhagic Critical Care and Intensive Care Medicine Rats Sprague-Dawley Ileum Internal medicine medicine Animals Mesenteric lymph nodes Infusions Intravenous Intensive care medicine Erythropoietin Saline Dose-Response Relationship Drug business.industry Peptide Fragments Rats Disease Models Animal Dose–response relationship Treatment Outcome medicine.anatomical_structure Endocrinology Shock (circulatory) Surgery medicine.symptom business Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Trauma: Injury, Infection & Critical Care. 71:S456-S461 |
| ISSN: | 0022-5282 |
| DOI: | 10.1097/ta.0b013e318232e782 |
| Popis: | BACKGROUND Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock. METHODS Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi-thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules. RESULTS At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g ± 111 CFU/g vs. 1130 CFU/g ± 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 μg/mL ± 0.31 μg/mL vs. 5.14 μg/mL ± 0.88 μg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group. CONCLUSION Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury. |
| Databáze: | OpenAIRE |
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